Combination Therapy for Rb-Negative Tumors

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Solution Overview

Problem

There is an ongoing need for improved compounds and methods to treat patients with Rb-negative cancers and abnormal cellular proliferative disorders, as existing treatments are ineffective due to the absence of the retinoblastoma tumor suppressor protein.

Innovation Solution

The use of a combination therapy involving a CDK4/6 inhibitor and a topoisomerase I inhibitor, which are administered together or alternately to a host, resulting in an advantageous anti-tumor effect compared to using either inhibitor alone.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If topoisomerase inhibitor is used to treat Rb-negative cancers, then anti-tumor effect is achieved, but development of secondary malignancies increases

Engineering Contradiction:

Improveanti-tumor effectVSAvoidsecondary malignancies

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines topoisomerase inhibitor with CDK4/6 inhibitor in a treatment regimen for Rb-negative cancers. This combination therapy achieves synergistic anti-tumor effects while allowing reduction of topoisomerase inhibitor dosage, thereby reducing the risk of secondary malignancies associated with high-dose topoisomerase inhibitor monotherapy

Inventive Principle:

Principle #5Merging (Combining)

2Ease of operation

If CDK4/6 inhibitor is used alone to treat Rb-negative cancers, then treatment is administered, but anti-tumor effect is insufficient

Engineering Contradiction:

Improvetreatment administrationVSAvoidanti-tumor effect

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent combines CDK4/6 inhibitor with topoisomerase inhibitor to create a synergistic treatment regimen. The CDK4/6 inhibitor blocks cell cycle progression at the G1/S transition, while the topoisomerase inhibitor causes DNA damage and prevents replication, together achieving superior anti-tumor effects compared to either agent alone

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If high dose topoisomerase inhibitor is used to maximize anti-tumor effect, then tumor control improves, but risk of secondary malignancies increases

Engineering Contradiction:

Improvetumor controlVSAvoidsecondary malignancy risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs combination therapy where topoisomerase inhibitor is used at reduced doses alongside CDK4/6 inhibitor. The CDK4/6 inhibitor provides additive anti-tumor activity through cell cycle arrest, allowing the topoisomerase inhibitor to be dosed at lower levels that reduce secondary malignancy risk while maintaining effective tumor control through synergistic mechanisms

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12285431B2Treatment of Rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors

Publication Date: 2025.04.29 PHARMACOSMOS HLDG AS

AI summary

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.